1. PHARMACOTHERAPY III PHCY 510
University of Nizwa
College of Pharmacy and Nursing
School of Pharmacy
PHARMACOTHERAPY III
PHCY 510
Lecture 1 Infectious Diseases “Antibiotic Regimen Selection” Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy, CPN University of Nizwa

2. Course Outcome
Upon completion of this lecture the students will be able to
recognize the sources, risk factors and common signs of infection,
identify the principles of antimicrobial use,
apply antimicrobial drug therapy selection process,
identify antibiotic resistance and its management.

3. Infectious Diseases
Infectious diseases are illnesses caused by bacteria, viruses, fungi or parasites.
Sources of infectious diseases are
coming in contact with a person or animal who has the infection.
contaminated food and water (an outbreak of a disease).
indirect contact with disease-causing organisms.
through insects or carriers (vectors).

4. Risk factors for getting infectious diseases
taking steroids or taking immunosuppressant medications.
has HIV or Cancer or other medical conditions like implanted medical devices, malnutrition and extremes of age.
Infectious diseases, like measles and chickenpox, can be prevented by vaccines.
Abscesses are collections of pus in small tissue spaces, usually caused by bacterial infection.
The presence of bacteria in the bloodstream is called Bacteremia causing septicemia (septic shock).

5. Identify the Presence of Infection
Fever defined as a controlled elevation of body temperature above normal range of 36.7 to 37.0°C (98.1 to 98.6°F) (measured orally).
Elevated white blood cell counts because of the mobilization of granulocytes and/or lymphocytes to destroy invading microbes.
The normal values for WBC counts is between 4,000 and 10,000/mm3.
Increase in bands (immature neutrophils).
Pain and inflammation may go along with infection and are sometimes shown by swelling, erythema, tenderness, and purulent drainage.
Bacterial infections are associated with elevated granulocyte counts (neutrophils, basophils), often with increased numbers of immature forms (band neutrophils) seen in peripheral blood smears (left-shift).

6. Identify the Source of Infection
Make an educated guess to what the infection is if you know the source.
Remove the source of infection if applicable.
Change indwelling intravenous lines or ports
Surgical removal of an abscess

8. Identify the Causative Pathogen
In case of suspected infection, culture specimens are obtained from suspected site to identify the pathogen(s) responsible.
Infected body materials must be sampled like
sputum for suspected pneumonia or a lung infection
a urine culture for cystitis (bladder) or pyelonephritis (kidney infection)
cerebrospinal fluid (CSF) for meningitis
Blood cultures should be performed in the acutely ill, febrile patient.

9. Abscesses and cellulitic areas should also be aspirated.
Caution must be used in the evaluation of positive culture results from normally sterile sites (e.g., blood, cerebrospinal fluid, joint fluid).
The recovery of bacteria normally found on the skin in large quantities (e.g., coagulase-negative staphylococci, diphtheroids) from one of these sites may be a result of contamination of the specimen rather than a true infection.
Culture and sensitivity testing are the next steps after staining techniques.
Not all bacterial organisms can be seen
or are distinguishable using Gram staining, particularly organisms
that grow intracellularly or do not have peptidoglycan-
containing cell walls. Determining an organism’s
Gram staining characteristics narrows the list of
potential pathogens and may assist in directing initial empiric
therapy.

10. Bacterial shapes and arrangements

11. Classification of Infectious Organisms
Microorganism
Class and subclass examples
Bacteria
Aerobic
Gram +ve
Cocci:
Streptococcus pneumonia,
Streptococcus viridans
Staphylococcus aureus,
Staphylococcus epidermidis
Enterococcus
Rods (bacilli):
Corynebacterium
Listeria
Gram ‐ve
Neisseria meningitides.
Neisseria gonorrhoeae.
Escherichia coli, Klebsiella pneumonia,
Pseudomonas aeruginosa
Helicobacter pylori
Haemophilus influenzae
Enterobacter, Citrobacter, Proteus,
Serratia, Salmonella, Shigella)
Campylobacter, Legionella
Anaerobic
Peptostreptococcus
Clostridium tetani,
Clostridium difficile
None
Bacteroides fragilis,
Fusobacterium

12. Microorganism
Examples
Mycobacteria [TB]
Mycobacterium tuberculosis
Mycobacterium avium
Acid‐Fast Stain (AFB)
Fungi
Aspergillus fumigatus, Candida Albicans, Cryptococcus neoformans, Histoplasma capsolatum, Tinea ringworm, Trichophyton
Viruses
Influenza, hepatitis A, B, C, D, E; human immunodeficiency virus (HIV); rubella; herpes; cytomegalovirus (CMV);
rhinovirus, adenovirus -Colds and Flu
Chlamydiae
Chlamydia trachomatis
Chlamydia pneumonia

13. SELECTION OF PRESUMPTIVE (Likely) THERAPY
The factors considered include
the severity and acuteness of the disease,
host factors,
factors related to the drugs used, and the necessity for use of multiple agents.
Generally accepted drugs of choice for treatment of most pathogens.
When selecting antimicrobial regimens, local susceptibility data should be considered.

14. Antimicrobial Drug Therapy Selection Process
Step 1
Establish the need for antimicrobial therapy.
Step 2
Attempt to identify the pathogen.
Step 3
Select empiric antimicrobial therapy.
Step 4
Monitor therapy for efficacy and toxicity.
Step 5
Refine antimicrobial therapy for definitive identification of
pathogen or infection

15. Selecting Antimicrobial Therapy
Empiric antibiotics, against potential pathogens, are initiated before the results of culture and sensitivity tests are available.
Waiting to administer antibiotics until results are available is not advisable.
May result in worsening of the patient’s condition or even death in the case of serious infections such as meningitis.

16. Empiric therapy generally treats a broad spectrum of potential pathogens, because most infectious diseases may be caused by a variety of microorganisms.
Patient characteristics such as age, immune status, and comorbid diseases, as well as the site of infection, are factors that influence potential pathogens.
Definitive or directed therapy (more patient-specific regimen) is determined for each patient when pathogenic organisms are identified and their antimicrobial susceptibility patterns are known.

17. Host Factors
When evaluating a patient for initial or empiric therapy, the following factors should be considered:
✓ Allergy or history of adverse drug reactions
✓ Age of patient
✓ Pregnancy
✓ Metabolic abnormalities
✓ Renal and hepatic function
✓ Concomitant drug therapy
Concomitant disease states.
Patients with diminished renal and/or hepatic function will accumulate certain drugs unless dosage is adjusted.

18. Drug Factors
Antibiotics may demonstrate concentration dependent (aminoglycosides and fluoroquinolones) or time-dependent (β-lactams) bactericidal effects.
The importance of tissue penetration varies with the site of infection.
Drugs that do not reach significant concentrations in cerebrospinal fluid should either be avoided or instilled directly when treating meningitis.

19. Combination Antimicrobial Therapy
used to broaden spectrum of coverage for empiric therapy,
achieve synergistic activity against the infecting organism,
prevent the emergence of resistance.
needed in mixed infections where multiple organisms are likely to be present, such as intraabdominal and female pelvic infections where a variety of aerobic and anaerobic bacteria may produce disease.

20. Synergism
Synergistic antimicrobial activity is advantageous for infections caused by gram-negative bacilli in immunosuppressed patients.
Combinations of aminoglycosides and β-lactams have been used since these drugs together generally act synergistically against a wide variety of bacteria.
Synergistic combinations may produce better results in infections caused by Pseudomonas aeruginosa, in certain infections caused by Enterococcus spp.

21. Disadvantages of Combination Therapy
increased cost
greater risk of drug toxicity
super infection with even more resistant bacteria
potential antagonistic actions
For example, agents that are capable of inducing β-lactamase production in bacteria (such as cefoxitin) may antagonize the effects of enzyme-labile drugs such as penicillins or imipenem.

22. Monitoring Therapeutic Response
Patients must be monitored carefully for a therapeutic response.
Culture and sensitivity reports from specimens collected must be reviewed.
Use of agents with the narrowest spectrum of activity against identified pathogens is recommended.
Patient monitoring should include a variety of parameters, including
white blood cell count
temperature
signs and symptoms of infection
appetite
radiologic studies as appropriate
determination of antimicrobial concentrations in body fluids

23. As the patient improves the route of antibiotic administration should be reevaluated.
Switch to oral therapy is an accepted practice for many infections.
Criteria favoring switch to oral therapy include:
✓ Overall clinical improvement
✓ Lack of fever for 8 to 24 hours
✓ Decreased WBC
✓ A functioning GI tract

24. Advantages of IV to Oral Antimicrobial conversion
Eliminates ADRs e.g. phlebitis (70% of cases)
Reduces catheter related infections (60% of cases)
Catheters should be removed within 72 h
Decreases the occurrence of nosocomial infections
Maintains patient’s comfort and motility
Reduces nursing and administration time
Facilitates sooner discharges / Reduce hospital stay
Reduces overall treatment cost

25. Failure of Antimicrobial Therapy
It is possible that the disease is not infectious or nonbacterial in origin, or there is an undetected pathogen.
Other factors include those directly related to drug selection, the host, or the pathogen.
Laboratory error in identification and/or susceptibility testing errors are rare.

26. Antibiotic Resistance
Patients’ Education
Educate patients through practice posters and
leaflets as antimicrobial prescribing is greatly
influenced by patients
Not for VIRUSES
Warning!
Unnecessary Antibiotics CAN be Harmful

27. Prescribers’ Education
Patients’ Education
Not for VIRUSES
Not of cold/flu/runny nose/sore throat
Complete the course
possible adverse effects of antibiotics,
nausea, diarrhea, stomach pain, possible allergic reactions, and vaginal yeast infections
Prescribers’ Education
Avoid prolonged course
Don't select a potent broad spectrum antimicrobial for simple infections
Don't add on antimicrobials regardless of culture-sensitivity data